Molecular dynamics (MD) simulations provide a unique atomic-level description of the structure and dynamics of proteins, which is essential for the mechanistic understanding of protein interactions and function in living organisms. However, traditional MD force fields that are optimized for folded proteins often generate overly compact structures and incorrect characteristics of intrinsically disordered proteins (IDPs) and protein regions (IDRs), thereby limiting the quantitative insights that can be gained from MD simulations. We introduce the residue-specific protein force field, ff99SBnmr2, which is derived from ff99SBnmr1 by balancing the backbone dihedral angle potentials in a residue-specific manner to quantitatively reproduce dihedral angle distributions from an experimental coil library. The new force field substantially improves the backbone conformational ensembles of disordered proteins, protein regions, and peptides while keeping well-defined protein structures stable and accurate. This balanced new force field should enable a myriad of applications that require quantitative descriptions of IDPs, IDRs, loop dynamics, and folding/unfolding equilibria in the presence and absence of interaction partners.

中文翻译：

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平衡的氨基酸特异性分子动力学力场，用于折叠和无序蛋白质的真实模拟。

分子动力学（MD）模拟为蛋白质的结构和动力学提供了独特的原子级描述，这对于机械理解生物体内蛋白质相互作用和功能至关重要。但是，针对折叠蛋白进行优化的传统MD力场通常会产生过于紧凑的结构以及固有无序蛋白（IDP）和蛋白区域（IDR）的错误特征，从而限制了可从MD模拟中获得的定量洞察力。我们介绍了特定于残基的蛋白质力场ff99SBnmr2，它是通过以特定于残基的方式平衡骨架二面角电位从ff99SBnmr1派生而来，以从实验线圈库中定量再现二面角分布。新的力场极大地改善了无序蛋白质，蛋白质区域和肽的骨架构象整体，同时保持了明确定义的蛋白质结构稳定和准确。这种平衡的新力场应可实现无数应用，这些应用需要在存在和不存在相互作用伙伴的情况下对IDP，IDR，回路动力学以及折叠/展开平衡进行定量描述。